Dynamic Optical Tomographic Imaging Devices Methods and Systems

ABSTRACT

The disclosed subject matter includes optical tomographic systems for acquiring and displaying dynamic data representing changes in a target tissue sample to external provocation. For example, the disclosed devices, methods and systems may be used for quantifying dynamic vascular changes caused by imposed blood pressure changes for diagnosing peripheral artery disease.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/294,086, filed Oct. 14, 2016, which is a continuation application ofU.S. patent application Ser. No. 13/876,861 filed Jun. 18, 2013, nowU.S. Pat. No. 9,492,089, issued on Nov. 15, 2016, which is a U.S.national stage filing under 35 U.S.C. § 371 of International ApplicationNo. PCT/US2011/060489 filed Nov. 11, 2011, which claims priority to andthe benefit of U.S. Provisional Application No. 61/412,717 filed Nov.11, 2010, the content of which are incorporated herein by reference intheir entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with government support under AR046255 awardedby the National Institutes of Health (NIH). The government has certainrights in the invention.

FIELD

The present disclosure relates generally to systems, devices, andmethods for tomographic imaging, and more particularly to systems,devices and methods for tomographic imaging for peripheral arterialdiseases.

BACKGROUND

Optical tomographic imaging uses signals from the amplitude attenuationor phase modification of light scattered by a tissue or sample. Injectedlight diffuses throughout a target and exits at the surface. Light canbe injected and received at multiple positions on a surface of a targetmaterial, such as body structure, and the received light used togenerate tomographic images. Amplitude attenuation and phase shift ofthe received light relative to can be used to resolve spatialinformation regarding the absorbing and scattering media in the target,for example, the spatial information can be presented in the form of avolumetric or cross-sectional image of the anatomy of a body part.

Peripheral Arterial Disease (PAD) is a highly prevalent atheroscleroticsyndrome that affects approximately 8 to 12 million individuals in theUnited States and is associated with significant morbidity andmortality. PAD is responsible for approximately 275,000 hospitaladmissions per year, as well as over 2,750,000 office visits per yearand approximately 45,000 deaths per year. PAD results from a variablecombination of changes in the intima of arteries consisting of focalaccumulation of lipids, complex carbohydrates, blood and blood products,fibrous tissue, calcium deposits. PAD also results from a build-up ofplaque on the inside of the arterial walls, inhibiting proper bloodsupply to organs. The prevalence of PAD increases significantly withage. In a large study that included 5,450 patients, the prevalence ofPAD based on the ankle-brachial index (ABI) increased from 9% ofsubjects 55-59 years of age to 57% of patients 85-89 years of age. Theprevalence of PAD does not change with the patient's gender.

PAD typically manifests itself early in the legs and foot and iscommonly referred to as lower extremity arterial disease (LEAD). Lowerextremity arterial disease (LEAD) is defined as decreased arterialperfusion to the lower extremities. LEAD is a common condition inindividuals with diabetes. LEAD in diabetes is compounded by thepresence of peripheral neuropathy and by susceptibility to infection.Peripheral neuropathy causes a lack of sensation in the upper and lowerperipheries leading to a patient's inability to feel cuts and bruises.Infections are thus more likely to occur.

If undetected, LEAD can progress to cause foot ulcerations, poor woundhealing, gangrene, and ultimately amputation. Detection of LEAD isdifficult, especially in patients with diabetes where calcification ofthe arteries and neuropathy alter the blood pressure measurements. Thecurrent techniques used to diagnose LEAD, such as the ankle-brachialindex (ABI), typically use compressible arteries in order to accuratelydetect LEAD, complicating diagnosis in many patients. Currently thestandard for identifying and treating occlusive LEAD in the arterialsystem is Digital Subtraction Angiography (DSA).

In DSA a contrast agent is injected intra-arterially to the patient andan image of the vasculature is obtained. However, this method of imagingis invasive and contrast media is nephrotoxic and therefore hazardous inpatients with significant medical co-morbidities. In addition, thepatient is exposed to ionizing radiation, which limits DSA's frequencyof use. Peripheral vascular measures used to assess LEAD are usuallyderived from non-imaging techniques. Palpation of the peripheral pulseshas been used as a clinical tool to assess occlusive LEAD in patients.However, the subjective nature of this method can lead to inconsistencyamongst physician evaluations. Factors such as temperature, anatomicalvariation and the physician's palpation technique can greatly alter thediagnosis. Some physicians also use pressure cuffs to determine arterialblood pressure.

LEAD can also be assessed with invasive procedures. For example, the useof arterial catheters for blood pressure monitoring. Although thesemethods are sensitive and accurate, invasive methods tend to be morecumbersome to use, and they generally bear greater risk of adverseeffects relative to non-invasive techniques. These factors alongside thehigher cost, limit the use of invasive techniques as a screening tool.

Measurement of the ankle brachial index (ABI) which is the ratio ofsystolic pressure measured at the dorsalis pedis or posterior tibialartery to the brachial systolic pressure is also used to evaluate LEAD.However, the progression of LEAD in diabetes patients is frequentlycompounded by neuropathy and heavy calcification of the arteries thatrenders them non-compressible. Furthermore, blood pressure readings atthe dorsalis pedis are often faint or in some cases absent. Pulse volumerecordings (PVR) utilize blood pressure cuffs inflated to 60 mmHg andare placed at the thigh, calf, and forefoot level, and the volume ofexpansion and contraction of the extremity is measured in order toaccurately gauge the amount of blood entering the extremity during thecardiac cycle. In the setting of arterial stenosis, PVR waveforms willbe diminished and this measuring tool is used to complement ABI inpatients with diabetes. However, PVR provides a more subjective ratherthan objective measure of the degree of arterial insufficiency.

LEAD can also be diagnosed using imaging methods such as velocimetry andcontinuous-wave Doppler ultrasound. The Doppler waveform obtained from anormal artery has a triphasic shape. However, measuring at an occludedlocation shows a waveform of increased velocity and bi- or monophasicbehavior. Unlike ABI, and TSP, velocimetry only provides a qualitativemeasure of occlusive LEAD in compressible arteries. In addition, Dopplerultrasound cannot be used on patients with diabetes and non-compressiblearteries because the pressures obtained in these patients are spuriouslyhigh. Due to the shortcomings of continuous wave Doppler ultrasound andABI/PVR, Duplex Ultrasound is frequently used to analyze the peripheralvasculature. Duplex Ultrasound is a combination conventional B-modeultrasound imaging with color Doppler and pulsed-wave Doppler waveformsampling. The limitations of duplex are that it fails to visualize up to13% of arterial segments in the calf and is operator dependent.

Thus, while X-ray and MM provide great anatomical detail they typicallydo not provide enough physiological detail and smaller arteries may notbe visualized or the artery may not have as much blood flow as expected.

SUMMARY

Optical tomography (OT) overcomes the limitations of current diagnostictechniques. The visible and near-infrared light used in the instrumenttypically has no adverse health effects and measurements can be repeatedfrequently. Furthermore, unlike X-ray angiography, which assesses bloodvessel occlusion and obstructions in blood flow, OT allows assessment ofthe vessel. In addition, the OT imaging systems can use less expensiveparts than X-ray instrumentation and can be scaled down to handheldportable systems. Therefore, OT imaging systems could be used at pointsof care as readily available screening devices.

Optical tomography can be used to detect the concentration of oxygenatedand deoxygenated hemoglobin as well as the total hemoglobinconcentration which is proportional to blood volume. Thesecharacteristics can be measured along with the absorption and scatteringcoefficients of the cross section being imaged. OT imaging is alsoindependent of the compressibility of the arteries, and does not requirethe use of contrast agents to obtain valuable information about theblood content within the imaged body part.

Moreover, since optical tomography offers various kinds of contrastinformation (e.g., oxyhemoglobin and deoxyhemoglobin concentrations,blood volume, tissue-scattering) it can be further used to complementinformation obtained through other types of imaging modalities.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings described herein are for illustration purposes only and arenot intended to limit the scope of the present disclosure in any way.The invention will be best understood by reading the ensuingspecification in conjunction with the drawing figures, in which likeelements are designated by like reference numerals. As used herein,various embodiments can mean some or all embodiments.

FIG. 1A shows a system for non-contact scanning of a target sample usinga camera for imaging emerging light from a body part and a laser scannerfor injecting photons into the body part. Although the example shownincludes elements for frequency modulating the light source and can beused for frequency domain optical tomography, with minor changes, asimilar arrangement is applicable to continuous wave or time resolvesshort pulsed optical tomography.

FIG. 1B shows another example of a frequency domain optical tomographysystem in which light is applied through a multiple optical fiberimaging system. The same configuration may also be used with continuouswave or time resolved short pulsed optical tomography.

FIG. 1C shows a modification of the system of FIG. 1B for continuouswave optical tomography.

FIG. 2 shows an optical interface module that supports an array ofoptical fibers including both light emitters and receivers in contact ornon-contact position to allow them to surround a body part such as aleg, arm, foot, finger, neck, or other body part to be investigated.

FIG. 3 shows the optical interface module of FIG. 2, sized for andarranged in position about a human ankle.

FIG. 4 shows an optical interface module that can be opened as aclamshell and which permits an axial spacing of respective ranks ofoptical fibers to be adjusted.

FIG. 5 shows an optical interface module that can be opened and closedabout a foot, for example the metatarsal region thereof, with a flatportion and an arching portion. The fiber supports may support fibersfor contact or non-contact arrangement over the body part.

FIG. 6 shows a single fiber support and an associated linear actuatorconfigured to move the end of the fiber to known position in contact ornon-contact relation to a body part. The feature of FIG. 6 is applicableto any of the embodiments disclosed.

FIG. 7 shows a method for scanning a body part including the control ofthe provocation of the body part (e.g. pressurizing the vasculaturetherewithin), and the acquisition of time series data, as well as thegeneration of image data and interactive display thereof.

FIGS. 8A through 9B show the temporal response of multiple detectorintensities at the finger and foot for a healthy person and a diabeticperson with peripheral vascular disease. The traces depict thetransmission profile over select detector channels for a singleillumination position at one wavelength each. The responses are plottedas a change in intensity versus time (minutes) and are normalized to arest period prior to provocation of the vasculature.

FIG. 10 illustrates a process and system for acquiring image data andpresenting the same to a user.

FIG. 11 shows an example of a computer processing system that can beused to implement the optical tomographic imaging methods describedherein. The system is applicable to any of the embodiments describedherein.

DETAILED DESCRIPTION

Embodiments of the present disclosure provide non-invasive opticaltomography imaging modalities that can be used to detect and monitorperipheral arterial disease (PAD) in the lower extremities. The imagingof peripheral hemodynamics in the lower extremities can efficientlydiagnose LEAD regardless of compressibility of the arteries, making itideal for diabetic patients. Optical tomography can also be used toimage vascular dynamics and blood flow patterns. Since in breast cancerand arthritis vascular changes are secondary effects, whereas in PADchanges in the vasculature are primary effects, the disclosed opticaltomography imaging modalities can be used to diagnose and monitorvascular diseases. The breast imaging systems can be used to gatherpreliminary data on diabetic patients with PAD. Differences betweenhealthy and diabetic PAD patients could be observed using thesepreliminary images.

FIG. 1A illustrates an optical tomography imaging system 100 used in oneembodiment. Frequency Domain Optical Tomography (FDOT) System: Thisfrequency domain instrument is based on the Picostar HR imager (LaVision GmbH). The light sources consist of laser diodes (Picoquant GmbH)that are modulated by a signal generator (Aeroflex Intl. Ltd.) atfrequencies up to 1 GHz. The laser light is coupled to an optical switchthat demultiplexes the light into various optical fibers which deliverthe light to different positions on an imaging geometry. Inside theimaging geometry resides the target to be imaged which will attenuatethe light and induce a phase shift based on its optical properties.Detector optical fibers collect light exiting the imaging geometry anddeliver the light to the Picostar imager. The detected light is incidenton an image intensifier (Kentech Instruments Ltd.) that is alsomodulated by a signal generator at frequencies up to 1 GHz in order todemodulate the detected light. The demodulated detected light ismeasured by a CCD camera. By using a CCD camera, light can is measuredin parallel from all detector fibers. By inducing phase shift betweenthe modulating action of the laser and the demodulating action of theintensifier, one can use the measure light at the respective phaseshifts in order to calculate the attenuation and phase shift induced bythe imaged target. The measured attenuation and phase shift at severalfrequencies between DC and 1 GHz, is input to a frequency domain opticaltomography reconstruction code in order to reconstruct the opticalproperties of the target. This system is currently being integrated withthe MRI machine (see 5) to allow for simultaneous optical and MR imagingof small animals.

The system 100 can include a laser source LD 1, such as, but not limitedto a laser diode, a laser diode driver 2, a signal generator 3 and 7, abody part (finger, foot, breast, etc.) placement area 4 for surface scanas well as trans-illuminating imaging, one or more lenses 5, an ICCDcamera, a high frequency imager 8, and a computer processing system 9 toimage body parts to produce cross section or volumetric images or rawtransmission data. The data may relate, for example, to the volume orflow of blood through the major arteries of the body part, such as,feet, fingers, or other extremities. In operation, the body part 4 isscanned simultaneously with light from the laser diode LD1 and a seconddiode LD2 (not shown).

Both laser diodes can be mounted on the same or separate scanningmechanisms, such as a gear-wheel, for example, so that slight movementsof the scanning mechanisms move the laser spot on the body part 4 to beimaged. In embodiments the laser may scan a line to acquire the surfacegeometry as explained below. Light from the same or a second diode LD1may be transmitted through the body part 4 and the detected lightintensity which is transmitted through the body part 4 captured by thecamera 6. The background may serve as calibration of the cameracoordinate system. The 3D surface coordinates are subsequently used togenerate a 3D finite element mesh. This mesh together with the lighttransmission measurements from the light detectors are input to an imagereconstruction algorithm that generates the cross-sections through theimaged body part.

FIG. 1B illustrates a frequency modulated optical tomographic system 200that can also be used to generate tomographic images of a body part 4.The frequency modulated tomography system 200 includes two laser diodes201, 202, generating light at two different wavelengths. Both laserdiodes 201 and 202 are driven by modulated laser drivers and both areconnected through optical fibers to a 2×32 fiber optic switch 203. Bothsource and detection fibers interface with the imaging geometry (e.g.,measuring module) 204 in which the body part is placed. Detection fibers221 that deliver light from the measuring module 204 have theirrespective tips of the fibers connected to the CCD camera 205. Thecamera images the fiber ends arrayed by the image intensifier 206. Theimage intensifier may or may not be used. Each laser diode 201 and 202can be modulated at a different frequency by signal generators 207 and208. The signal generators may be used to modulate the laser diodes 201,202 as well as a photocathode of the image intensifier 206. Theparameters of the generated signals (amplitude, frequency, phase, etc.)can be controlled by a computer processor CPU 209. The fiber opticsswitch 203 redirects the light from the two laser diodes 201, 202 insuccession to the array of source optical fibers that deliver the lightto fixed locations positioned around the measuring module. The lighttransmitted through the body part is carried by the detection opticalfibers into the image intensifier 206. The source optical fibers 222 areoptically coupled in pairs at different positions around the measuringmodule 204 to sample the body part at two different frequencies. Areference fiber 223 is also connected between the fiber switch 203 andthe image intensifier 206. The signal from one of the signal generators207 is input to both of the modulated laser diodes 201 and 202, whereasthe input from the second signal generator is input only to the imageintensifier 206. The frequency of the second signal generator 208 can bethe same as the first signal generator 207 and the phase differencesresulting between the two signals can be adjusted by the CPU 209. Usingthis set-up, the signals in respective pixels of the CCD depend on thephase difference. The source fibers serially illuminate the body part atdiscrete phase offsets.

FIG. 1C illustrates a continuous wave tomography system 300 includes twolaser diodes 301, 302, generating light at two different wavelengths.Both laser diodes 301, 302 are connected through optical fibers to afiber optic switch 303. Both source and detection fibers interface withthe imaging geometry (e.g., the measuring module) 304 in which the bodypart is placed. Detection fibers 321 that deliver light from themeasuring module 304 have their respective tips of the fibers directedto the CCD camera 305 by the image array 307 which supports the fibersin known positions so their respective signals can be demultiplexed fromthe image of the camera. The parameters of the generated signals can becontrolled by a computer processor CPU 314. The fiber optics switch 303redirects the light from the two laser diodes 301, 302 in succession tothe array of source optical fibers 322 that deliver the light to fixedlocations positioned around the imaging geometry 304. The source opticalfibers 322 are coupled in pairs at different positions around theimaging geometry 304 to sample the body part. The light transmittedthrough the body part is carried by the detection optical fibers toimage array 307.

The imaging systems 100-300 can include various types of measuringmodule for bringing the illuminating light source such as a fiber intocontact with the body part to be imaged (or projecting light onto thesurface of a body part), and then bringing the detected light from thebody part to the camera 6 or other photo detector. This may beaccomplished with optical fibers, which either make direct contact withthe body part, or are brought close to the body part in a simple, fixedgeometry. In the case that the optical fibers do not make direct contactwith the body part, an optical matching fluid (such as intralipid) maybe used to direct the light from the fiber tip to the surface of thebody part.

In order to create full 3D images of the entire imaged body part, thesource optical fibers and the detection optical fibers that deliver andcollect light from the entire body part are positioned around the bodypart, so that the tips of the source optical fibers and the tips of thedetection optical fibers are adjacent to and are surrounding the bodypart. The light is effectively scanned over the body part bysequentially emitting light from one light source at the time anddetecting the light intensity which is transmitted through the body partby the light detectors. One emitter may operate at a given time whileall the receivers receive light scattered from the emitter. Then anotheremitter may be activated and so on. The light of different frequencies(color) may be injected simultaneously and demultiplexed to providehigher temporal resolution. Acquired or predicted 3D surface coordinatesare used to generate a 3D finite element mesh. This mesh together withthe light transmission measurements from the light detectors are inputto an image reconstruction algorithm that generates the cross-sectionsthrough the imaged body part.

In the embodiment of FIG. 2, a measuring module 30 is used to image afinger 31 (not shown). The measuring module 30 includes a cylindricalbody 32 into which the finger can comfortably slide and which acts tostabilize the finger throughout the imaging process. The measuringmodule 30 encircles a portion of the cylindrical body 32 so that theactual finger can be positioned inside the measuring module 30. Aplurality of source and detection optical fibers 33 positioned in twoseparate rows are detachable attached to the measuring module 30 aroundthe perimeter of the imaging module 30 Each row can include up to 24optical fibers. The size of the measuring module 30 can be changed toaccommodate fingers of various shapes and sizes. NIR light is deliveredto the surface of the finger 31 through one fiber at the time (i.e.,source optical fiber) and the transmitted light intensities are measuredby all other optical fibers (i.e., detection optical fibers). Thecaptured transmission data is delivered to the photodetector for furtherprocessing. Using image reconstruction software, the detectedtransmitted light data can be used to generate three-dimensional crosssectional images of the body part.

A measuring module 11 is shown in FIG. 3. In this embodiment, the bodypart that is being imaged is the lower part of a leg 20. The measuringmodule 11 can be a cuff-shaped device that rises a few inches above theankle and is configured to accommodate various leg 20 sizes while stillkeeping the relative source-detector fiber 13 positions constant. Themeasuring module 11 includes a plurality of source optical fibers 13 anddetection optical fibers 13 detachably attached to the cuff-like deviceand arranged in at least two layers around the cuff-like device 11 so asto encircle the lower part of the leg 12 and so that when in use, thesource and detector fibers 13 deliver near-infrared (NIR) light to themajor arteries of the leg 12, and deliver the light transmitted throughthe major arteries of the leg 12 to the photodetector.

Each source and detector fiber 13 can be connected to a light conduit 14to deliver light from the laser source of an optical tomography systems28, which could be any one of systems 100-300, for example, to the bodypart 12 and to deliver transmitted light from the body part 12 to thephotodetector of the optical tomography system 28, which can be any oneof the optical tomography systems 100-300. The measuring module 11 isconfigured to be variable in size so that any size leg 12 can becomfortably fitted inside the measuring module 11.

The measuring module 11 can target the response around the dorsalispedis artery, the response of the posterior tibial artery, as well asthe response across the calf to measure the perfusion at an elevatedlocation on the lower extremities. The source optical fibers and thedetection optical fibers in the measuring module 11 can be positioned soas to surround a major artery of the lower leg 12. In operation, afterthe patient places a leg 12 inside the measuring module 11, the module11 can be filled with a matching liquid to overcome the gap between thefoot 12 and the source and detection optical fibers 13. The matchingliquid can help to overcome mismatches between the measuring module 11,and the leg 12 being imaged.

Visible and near-infrared (NIR) light is guided through the opticalfiber conduits 14 to the surface of the leg 12 under investigation. Eachof the source optical fibers 13 sequentially delivers light to the majorarteries in the leg 12 while each of the detection optical fibers 13capture the light transmitted through the arteries at various locations.The specific geometry between the source optical fibers and thedetection optical fibers allows the detection optical fibers to capturereflected and transmitted light through the major arteries of the leg12. The captured transmission data is then delivered to thephotodetector for further processing.

Using image reconstruction software, the detected transmitted light datacan be used to generate three-dimensional cross sectional images of thebody part. In order to determine whether there are any changes in thevasculature of the body part imaged or in the oxy and deoxy-hemoglobinor in the main protein in blood, a second set of transmission data andcorresponding second set of images are generated after an externalstimulus is applied to the imaged body part. The stimulus can begenerated by applying an external pressure on the body part using apressurizing device, such as but not limited to, a sphygmomanometer cuff18 placed around the body part 12.

After the application of the stimulus, a second set of transmission dataare taken and a second set of tomographic images are reconstructed usingthe same imaging and reconstruction methods as used for the generatingof the first set of data and images. The cuff 18 is activated to exertpressure on the leg 12 by a cuff actuator 42. The amount of pressureexerted by the cuff 18, as well as the timing of sequential release ofpressure is controlled by a controller 40. The controller is operativelyconnected to the cuff actuator 42 as well as the system 28.

Each set of transmission data and reconstructed images includeinformation regarding optical properties (reflection, absorption,scattering) of the imaged body part. From these optical properties,parameters such as perfusion rates, oxy and deoxy hemoglobinconcentrations, as well as blood volume can also be determined. Bycomparing the transmission data and the images in the first set withcorresponding transmission data and images in the second set, biomarkerssuch as, but not limited to, distribution of optical properties,perfusion rates, and differences in oxy and deoxy hemoglobinconcentrations can be ascertained. These biomarkers can then be used todifferentiate between a sick and a healthy patient. The opticaltomography system 28 may have a controller 40 which operates the cuffand OT system to perform an end to end diagnostic sequence.

In the embodiment of FIG. 4, a cuff-like measuring module 20 is shown.The cuff-like measuring module 20 can include a plurality (three shown)of adjustable rings 22-24, each including a plurality of source opticalfibers and detection optical fibers positioned around a surface of thering. The cuff-like measuring module 20 is adjustable in diameter inorder to accommodate various leg sizes and can open similar to ahandcuff for easy attachment and detachment. Each of the rings includestwo separate parts linked together using bracket type connecting members27, which when positioned in a first locked position, securely lock therings 22-24 together, and when in a second unlocked position, the ringsmay be moved in the axial (Z axis) direction relative to each other tochange the mutual spacing of the rings. The rings can also be opened bymeans of a clasp 29. The brackets may include a plurality of engagingsurfaces, to act as stops, positioned along the length of the brackets27 to allow the rings to be securely positioned in different positionsalong the length of the bracket when in the desired position. The rings22-24 are detachably attached to the brackets 22 to render a boot-likedevice 20. Each ring 22-24 can be placed strategically around the lowerextremity of the leg 12 to encircle the major arteries in the desiredportion of the leg 12. The width of the measuring module 20 as well asthe measuring rings 22-24 can be adjusted to accommodate different legsizes. The rings 22-24 can be placed around the metatarsals and theankle as well as the calf to obtain the hemodynamic response in themajor arteries and its surroundings and that of a higher portion of thelower extremity. The rings 22-24 can also move in a vertical direction Zso as to be able to be positioned at any desired height on the measuringmodule 20 and around the body part 12. The rings 22-24 with the opticalfibers distributed around the ring detect the transmission andreflectance of light through the arteries of the leg 12.

This design may employ an optical spacer but may also instead allow theoptical fibers to make direct contact with the skin and still maintainconstant source-detector fiber positions. In case the design does nothave a constant geometry, a robust image reconstruction technique calledthe Normalized Differentiation Method (NDM) can be used to reconstructthe images. This reconstruction algorithm can take the differencebetween a baseline optical measurement and the optical responsemeasurement relative to a stimulus. This method can reconstruct thedifference/relative optical properties instead of absolute opticalproperties and is therefore not nearly as dependent on the boundaryconditions and the source detector optical fiber positions.

The measuring modules 11 and 20 can target the response around thedorsalis pedis artery, the response of the posterior tibial artery, aswell as the response across the calf to measure the perfusion at anelevated location on the lower extremities. The source optical fibersand the detection optical fibers in both measuring modules 11 and 20 canbe positioned so as to surround a major artery of the lower leg 12.

In operation, after the patient places a leg 12 inside the boot 11 or20, the boot can be filled with a matching liquid to overcome the gapbetween the foot 12 and the source and detection optical fibers 13. Thematching liquid can help to overcome mismatches between the measuringmodule 11, 20, and the leg 12 being imaged. Visible and near-infrared(NIR) light is guided through the optical fiber conduits 14 to thesurface of the leg 12 under investigation. Each of the source opticalfibers 13 sequentially delivers light to the major arteries in the leg12 while each of the detection optical fibers 13 capture the lighttransmitted through the arteries at various locations. The specificgeometry between the source optical fibers and the detection opticalfibers allows the detection optical fibers to capture reflected andtransmitted light through the major arteries of the leg 12. The capturedtransmission data is then delivered to the photodetector for furtherprocessing. Using image reconstruction software, the detectedtransmitted light data can be used to generate three-dimensional crosssectional images of the body part.

The constant geometry of the source fibers and detection fibers aroundthe measuring modules may facilitate reconstruction of these opticalimages, because of the precise locations of the source and detectionfibers are known along the boundaries of the measuring modules 11 and30. Various reconstruction algorithms can be used to generate theimages, such as, but not limited to model based iterative imagereconstruction algorithms, diffusion-based algorithms, and transporttheory reconstruction algorithms.

FIG. 5 shows an optical interface module that can be opened and closedabout a foot 340, for example the metatarsal region thereof, with a flatportion 352, which acts as a base upon which the patient can stand. Theoptical interface modules also have an arching portion 344. Both thebase 352 and arching portion 344 support fibers (locations thereofindicated at 346 and 350) for transmitting and receiving light signals.The fiber supports may support fibers for contact or non-contactarrangement over the body part. The arching portion may be attached by ahinge 345 to allow the arching portion 344 to be positioned over thefoot. A latch 348 to hold the arching portion 344 firmly, once closed,may be provided. A cuff 342 may be provided for provoking thevasculature of the foot.

FIG. 6 shows a single fiber support 362, 368 and an associated linearactuator 364 configured to move the end of the fiber 366 to knownposition in contact or non-contact relation to a body part. The featureof FIG. 6 is applicable to any of the embodiments disclosed. Acontroller as in any of the embodiments described herein may be used toposition each of the fiber ends to a desired position automaticallybased on acquired or predicted surface geometry as described elsewhereherein. By knowing the precise position of the actuator and the support,the position of the fiber end may be known. Even if the fiber end, incontact with the skin, obscures the body part, the shape of the anatomymay be inferred by knowing the precise position of the fiber end if itis assumed the skin conforms to it. Such actuators may be provided, forexample, in the apparatus of FIG. 5 or any others compatible devices.

In alternative embodiments, the linear actuator may be replaced by amovable support with a spring that permits the light guide to movepassively therewithin. The support may further include an encoder toindicate a position of the light guide relative to the support. Theinformation from the encoder may be used to form the mesh.

Referring now to FIGS. 7 and 10, in a relevant embodiment, at S10 a bodypart such as a foot is surface scanned, imaged (photographed frommultiple angles, for example) to derive raw data from which a 3 surfacemodel can be generated. Alternatively a predicted surface is used, forexample, by drawing from a library of stored template for differentanatomical archetypes.

To obtain the geometry for image reconstructions, a photograph of thefoot or a laser scan surface geometry acquisition system may be used.Adjacent objects may be provided to give a reference to obtain preciseabsolute dimensional data. The surface geometry information may be usedto create a boundary and locate the sources and detectors. Inembodiments in which one or more actuators position the fiber ends intoknown positions in contact with the body part, the known positions andsizes of the fiber ends are used in determining the surface geometry.The process is illustrated figuratively in FIG. 10 where a camera 272images a foot 270 which is scanned by a laser 268 to acquire the surfacegeometry indicated at 282.

At S14 the body part is positioned in the imaging device (283 of FIG.10). Alternatively, the body part may already be positioned in theimaging device if concurrent surface geometry acquisition is done whilepositioned therein. The latter may be the case where a device such asnon-contact imaging is done or where the positions of the fibers incontact with the body can be obtained directly such as with the actuatorof FIG. 6.

Optical transmission measurements on the body part, such as the foot,are begun at S16. In embodiments, these may be performed with a digitalnear-infrared optical tomography imager. In that case, a combinedoptical beam consisting of two laser diodes (wavelength λ, =765 nm and830 nm) may act as illuminating sources. The sources may be sequentiallycoupled into different 1 mm multimode fiber bundles that distributelight to multiple areas along the measurement probe. The measurementprobe may have any number of fiber supports that hold optical fibersclose to or in contact with the surface of the body part such as a foot.For example, the device of FIG. 5 may be used.

The current of each laser diode may be modulated to a distinct amplitudeand frequency. In this way, multiple wavelengths may be illuminatedsimultaneously, and their respective amplitude and phase contribution onthe attenuated detected signal can be extracted using synchronousdetection techniques. The total power incident on the target may be, forexample, about 30 mW. Once the light is attenuated as it propagatesthrough the body part, it then exits the probe and is collected by thevarious fiber bundles positioned around the target for a fibermultiplexing scheme. As described here and elsewhere other schemes foroptical tomography transmission measurements are also possible, forexample, non-contact using imaging as in FIG. 1, without the use offiber multiplexing. In an exemplary embodiment, a total of 34 fibers maybe brought in contact with the foot with 14 serving as light sources and20 as detection fibers.

At S12, in parallel or series with other steps, a mesh may be generatedusing the data from the surface geometry 282 and or a priori informationof anatomy (or patient-specific documentation such as medical imagingstudies). For example, a two dimensional mesh of a foot (FIG. 10, 308)may be generated. Alternatively a three-dimension mesh may be generated.

At S17, a provocation is induced in the body part. For example, the flowthrough the vasculature may be modified using a pressure cuff that isapplied proximally of the imaging module, for example, to the upperthigh. Initially, a baseline measurement may be taken, for example, foran interval of approximately 1 minute and data recorded for thegeneration of multiple image frames, for example, 400 frames. Next, thepressure cuff may be inflated to a first pressure, for example toproduce a venous occlusion (for example, 60 mmHg)/The pressure may bemaintained for an interval while data is acquired continuously (forexample, 1.5 minutes) at which point the pressure may be released togenerate a rest interval during which data is also recorded. Asindicated at S18, a number of additional provocations may be inducedwith continuous data acquisition for the generation of time seriesimaging (or non-imaging) data during each and in the interval between.For example, an increased pressure of 120 mmHg for arterial occlusionmay be applied to a proximal cuff with a following rest period, theintervals being the same as for the venous occlusion. The provocationsmay be repeated multiple times, for example three times, to confirmrepeatability, for statistical analysis or for merging data for randomerror filtering.

At S20 the data are processed by system (FIG. 10, 284) for display. Forexample, to generate two-dimensional reconstructions of the opticalproperties of a body part such as the foot, a transport-theory-basedPDE-constrained multispectral image reconstruction scheme may be used toreconstruct the spatial distributions of the oxy and deoxy-hemoglobinconcentrations in the foot. For this purpose, the differences in Hlb021and [Hb] obtained through reconstruction is relative to baseline whichmay be assumed to be given by Hlb021=23.4306 μM1 and [Hb]=14.6874 μM1,throughout the body part. A radial basis function (RBF)-typeregularization scheme may be employed to obtain quality images byreducing noise and artifacts near the foot surface.

In an actual example, the observed signal changes corresponded tounderstandable physiologic responses in a foot and finger. FIGS. 8Athrough 9B show the temporal response of multiple detector intensitiesat the finger (FIGS. 8A and 8B) and foot (FIGS. 9A and 9B) for a healthyperson (FIGS. 8A and 9A) and a diabetic person with peripheral vasculardisease (FIGS. 8B and 9B). The traces 301 depict the transmissionprofiles over respective detector channels for a single illuminationposition at one wavelength each. The responses are plotted as a changein intensity versus time (minutes) and are normalized to a rest periodprior to provocation of the vasculature. When the first pressure cuff (@60 mmHg) is applied to a healthy volunteer, venous return is inhibitedwhile arterial supply is still active, causing blood to pool in the leg.As a result, the optical attenuation absorption increases causing adecline in transmitted intensities. Subsequent to the pressure beingreleased, the accumulated blood volume begins to diminish, at firstrapidly, due to the elevated pressure gradient in the vascular system,and then more gradually as the gradient eases toward equilibrium and theoptical signal returns towards baseline. When the cuff is reapplied(e.g., at 120 mmHg) the signal magnitude drops even further relative tothe initial value, indicating a more complete venous occlusion. The timetraces of patients with PAD show significantly different behaviors fromthose of a healthy volunteer. While in all the cases a drop intransmitted intensities is observed upon application of the pressurecuff, the drops of the PAD patients are much smaller in magnitude (15%)than the healthy volunteer. In addition, in both PAD cases the occlusionand recovery rate appear to be almost linear, however the healthyvolunteer's rates show a more exponential profile.

In an example embodiment, the transmission and surface data may beprocessed to reconstruct and display 304 a section view 306 of the bodypart in which the concentration or volumes of interest are suitablyhighlighted 307. For example, the HbT concentrations in the arteries ofthe foot may be shown with a color or luminance channel indicating theamount or properties of blood (e.g., oxygenation). In an embodiment, thedisplay interface may permit the selection of a particular part (e.g., apixel) for which selected part the time trace of the target property maybe displayed as indicated at 306 in display 302. For example, a cursor309 may be provided for this purpose. A reference 308 trace (healthy)may be superimposed on the measured trace 311 (PAD) for comparison. Thereference trace may be selected from a library and may representstatistics of classes of pathology or other groups.

The finger results above are from a study in which an arm cuff was usedto provoke the finger vasculature. Actual observations by the inventorsshow that the ankle brachial index (ABI) can easily distinguish betweenthe healthy subjects and PAD patient but in some cases the differencesare not clear. A healthy volunteer and a patient with both diabetes andPAD can have very similar ABI measurements. Yet the optical transmissiontraces clearly show a compromised vasculature in the observed cases,indicating that optical methods may provide a more reliable test for PADin patients with diabetes than ABI.

Model based iterative algorithms (MOBIR) typically include threeelements, such as a forward model, an objective function, and anupdating scheme The forward model can give a numerical solution of thelight distribution inside the object Ω and predicts the measurements(energy radiance Ψ_(d)) on the boundary ∂Ω. To predict these measurementone can provide the source strength S(r_(s)), the source positions r_(s)and an initial guess of the optical biomarkersμ₀=[μ_(s,0)(r),μ_(a,0)(r)]. A given set of measurements M on theboundary ∂Ω can then be compared with the set of the predicted radiancesΨ_(d)(μ₀) by defining an objective function Φ. A simple example caninclude the least square error norm between measured and predicted datagiven by

$\begin{matrix}{\Phi = {\sum\limits_{s}{\sum\limits_{d}{( {M_{s,d} - {\Psi_{s,d}(\mu)}} )^{2}/\sigma^{2}}}}} & (1)\end{matrix}$

An updating scheme can be employed that provides a new guess of opticalbiomarkers μ₀+Δμ, which reduce the value of the objective function Φ. Anew forward calculation can be performed based on the new set of opticalbiomarkers μ₀+Δμ. The iteration process can be finished when the minimumof the objective function is reached within a specified error. At thispoint the predicted detector readings can be identical to the measureddetector readings within a given tolerance. The optical biomarkers, canbe mapped into a two or three-dimensional image.

Algorithms differ in the way updates are obtained, how the objectivefunction is defined and what forward model is used. While changing theupdating scheme can affect the convergence speed of a code, changing theobjective function or the forward model can affect the accuracy of thereconstruction result. As a forward model most groups use the diffusionequation given by

$\begin{matrix}{{( {{\frac{1}{c}\frac{\partial}{\partial t}} + {\mu_{a}(r)} - {\nabla( {{D(r)}\nabla} )}} ){\varphi ( {r,t} )}} = {{S( {r,t} )}.}} & (2)\end{matrix}$

Using finite-difference, finite-element, or analytical solution,predictions of the fluence (energy per unit area) on the surface of themedium are made.

The diffusion based algorithm can be an approximation of the moregenerally applicable integro-differential equation of radiative transfer(ERT), given by

$\begin{matrix}{{{\Omega \; {\nabla{\Psi ( {r,\Omega} )}}} + {( {\mu_{a} + \mu_{s}} ){\Psi ( {r,\Omega} )}}} = {{S( {r,\Omega} )} + {\mu_{s}{\int\limits_{4\; \pi}{{p( {\Omega,\Omega^{\prime}} )}{\Psi ( {r,\Omega^{\prime}} )}d\; {\Omega^{\prime}.}}}}}} & (3)\end{matrix}$

In cases where the diffusion approximation is not valid, using thisapproximation can lead to erroneous prediction of the measurements.

Diffusion-based calculations can predict an almost constant fluence ratein the area of the fluid. The calculations based on the theory ofradiative transport can predict a different distribution of light withinthe medium. The differences in the forward model can directly influencethe accuracy of the reconstruction. For example, if for a givendistribution of optical properties, the diffusion model predicts ahigher signal at a detector than actually measured, the reconstructionscheme can lower absorption and/or scattering coefficients in certainareas. In general the diffusion approximation is not as accurate whensmall sample geometries are considered in which source-detectorseparations are small and boundaries effects are dominant.

The transport theory can be more accurate when the medium containsregions in which the absorption coefficient is not much smaller than thescattering coefficient or when regions are considered in which thescattering and absorption are very low (so-called void-like regions),such as cerebrospinal-fluid-filled spaces in the brain, or thesynovial-fluid-filled space in joints.

In order to determine whether there are any changes in the vasculatureof the body part imaged or in the oxy and deoxy-hemoglobin or in themain protein in blood, a second set of transmission data andcorresponding second set of images are generated after an externalstimulus is applied to the imaged body part. The stimulus can begenerated by applying an external pressure on the body part using apressurizing device, such as but not limited to, a sphygmomanometer cuffplaced around the body part. After the application of the stimulus, asecond set of transmission data are taken and a second set oftomographic images are reconstructed using the same imaging andreconstruction methods as used for the generating of the first set ofdata and images.

Each set of transmission data and reconstructed images includeinformation regarding optical properties (reflection, absorption,scattering) of the imaged body part. From these optical properties,parameters such as perfusion rates, oxy and deoxy hemoglobinconcentrations, as well as blood volume can also be determined. Bycomparing the transmission data and the images in the first set withcorresponding transmission data and images in the second set, biomarkerssuch as, but not limited to, distribution of optical properties,perfusion rates, and differences in oxy and deoxy hemoglobinconcentrations can be ascertained. These biomarkers can then be used todifferentiate between a sick and a healthy patient.

Multiple response characteristics can be defined that serve todiscriminate healthy tissue from diseased tissue. For example, theminimum and maximum absorption coefficients, the ratio between theminimum and maximum absorption coefficients, the smallest and largestabsorption and scattering coefficients, the ratios of thesecoefficients, and the variance of the absorption and scatteringcoefficients. Differences in these optically derived biomarkers can allbe used individually or in combination to classify and monitor patients.For example, the absorption coefficient (μa) decreases in patients withLEAD because of the decreased amount of blood flowing in the arteries,and thus the magnitude in the decrease of (μa) may be proportional tothe degree of the patient's LEAD. Further, the oxygenated hemoglobintrace may recover at a slower rate in patients with LEAD because thearteries may not be able to supply the oxygenated blood as quickly aspatients with no occlusions in their arteries. The total hemoglobinconcentration and total blood volume may also decrease for patients withLEAD because of the decrease in blood flowing through the arteries ofthe sick patients. Therefore, monitoring these biomarkers can enable thephysicians to accurately diagnose the degree of PAD or LEAD by detectingthe physiological change in the hemoglobin and the change in the opticalproperties of the vasculature with respect to the stimulus.

The image based biomarkers extracted from the first and second sets ofoptical tomography images can be used individually and in combinationwith other biomarkers to further increase the accuracy of the system indetermining whether a patient is healthy or has PAD or LEAD. Inaddition, the results obtained using the tomographic imaging modalitiesas described above can also be used together with results obtained usingother existing technologies to allow earlier and more appropriateintervention to treat this debilitating condition. For example, resultsobtained using ankle-brachial index (ABI) as well as that of DuplexUltrasound scans, which are considered the standard techniques, can beused together with the results obtained using the tomographic imagingmodality described above.

The data can also be reconstructed in order to obtain the differences inthe metabolic activity in the joints, for example. By using dataobtained using two wavelengths, the fluctuation in the oxygenated anddeoxygenated hemoglobin concentrations for the finger joints can also beobtained. The spatial distribution of the fllb021, [Hb] and [MT] infinger joints of healthy patients and patients with rheumatoid arthritisare markedly different. A ring structure is evident a healthy patient, avoid-like center region shrinks until it is completely lost and theentire joint cavity is inflamed. A high metabolic rate activity can alsobe seen. Since the total hemoglobin concentration can be directlyproportional to blood volume, this data can also be used to determineblood volume.

A similar protocol can be used to study the feet. Patients can havetheir ABI measured first, which is the ratio of the systolic pressuremeasured at the dorsalis pedis or posterior tibial artery to that of thebrachial systolic pressure. Patients can place their foot inside themeasuring module to target the major arteries of the foot. Then apressure cuff can be placed around the patient's thigh. A baselinemeasurement can be taken and then pressure can be applied to the thighuntil it constricts the venous return, while arteries can still beflowing blood to the lower extremities. The pressure can then bereleased for a rest period and then the cuff reapplied with strongerforce to shut off both venous return and arterial supply. During themeasurements, the patients can have multiple cuffs around their legs tocompress the arteries.

The temporal response of the detector intensities can be used toreconstruct the data to obtain the spatial maps of the hemoglobinresponse of the foot cross sections that contain the dorsalis pedis andthe posterior tibial artery. The same exemplary experiment can berepeated with a heated pad added at the measuring site in order toinduce vasodilatation. The difference in the responses to the variousstimuli can be used as signatures to diagnose LEAD in both diabetics andnon-diabetic patients. The absorption coefficient (μa) may decrease inpatients with LEAD because of the decreased amount of blood flowing inthe arteries. The magnitude in the decrease of (μa) can be proportionalto the degree of the patient's LEAD and these findings can be validatedwith the ABI measurements and ultrasound scan. The total hemoglobinconcentration and total blood volume may also decrease for patients withLEAD because of the decrease in blood flowing through the arteries ofthe sick patients.

An alternative system that can be used is a frequency domain opticaltomography system. This optical tomography system is capable of usinghigh modulation frequencies up to 1 GHz, which allow for betterseparation of absorption and scattering and more accuratereconstructions.

To characterize the efficacy of optical tomography in identifying LEADthe sensitivity and specificity can also be determined. The resultsobtained can be compared with those of the ankle-brachial index (ABI) aswell as that of Duplex Ultrasound. These are non-invasive diagnostictechniques that are currently used on patients suspected to have LEAD,before resorting to digital subtraction angiography. These diagnostictechniques can be used as standards, and differences in mean values andstandard deviation of various optically derived classifiers that can beused to distinguish between diseased and healthy vasculature can besought.

The ABI is a quantitative method for detecting lower extremity arterialdisease. The optical images show different stages of LEAD. Table 1 showsthe ABI measurements associated with mild, moderate and severe LEAD aswell as those for patients with non-compressible arteries and healthypatients. One of the key advantages of optical tomography is that it iscapable of imaging calcified arteries which are not diagnosable with ABImeasurements.

TABLE 1 Degree of LEAD ABI Healthy Control 0.91-1.30 Mild LEAD 0.70-0.90Moderate LEAD 0.41-0.69 Severe LEAD/Critical <0.4 Limb IschemiaNon-compressible >1.31

The other imaging modality that can be considered for comparison withoptical tomography is Duplex ultrasound. Duplex ultrasound is commonlyused in clinical settings to detect LEAD. Ultrasound however has a lotof operator dependent variables that affect its efficacy at detectingLEAD. In addition, ultrasound cannot provide reliable imaging if thereare poor acoustic windows (e.g., bowel gas attenuation, diffuse vascularcalcification, or metallic stents) or poor intrinsic echogenicity of thetissues. The ultrasound also only provides qualitative measurementswhich could vary in interpretation depending on the physician making thediagnosis. The ultrasound measurements can be grouped into 4 categoriessimilar to the ABI measurements: healthy control, mild LEAD, moderateLEAD and severe LEAD. They can be compared with the optical tomographyimages of the same patients to determine the optical tomography imagingmodality's sensitivity and specificity.

Several biomarkers can be acquired from optical tomography images takenduring the clinical study and each parameter can be used individuallyand in combination with other biomarkers to determine if the patient hasLEAD. To combine these biomarkers an analysis under a vectorquantization based classification called Self-Organizing Mapping (SOM)can be used. SOM is an unsupervised learning method, with the purpose oftransforming a feature vector of arbitrary dimension drawn from thegiven feature space into simplified generally 2D discrete maps. Thismethod can allow producing multivariate receiver operatingcharacteristic (ROC) curves from which sensitivity and specificities canbe determined. Parameter combinations can lead to higher sensitivitieswhen compared to single parameter classifications. The data can also beseparated for patients with LEAD and those with LEAD and diabetes inorder to examine if the biomarkers that maximize the accuracy of thediagnosis as defined by sensitivity and specificity.

FIG. 11 shows an example of a computer processing system that can beused to implement the optical tomographic imaging methods describedherein. For example, the imaging methods can be performed by aprocessing arrangement and/or a computing arrangement 101. Suchprocessing/computing arrangement 101 can be, e.g., entirely or a partof, or include, but not limited to, a computer/processor 102 that caninclude, e.g., one or more microprocessors, and use instructions storedon a computer-accessible medium (e.g., RAM, ROM, hard drive, or otherstorage device).

A computer-accessible medium 103 (e.g., as described herein above, astorage device such as a hard disk, floppy disk, memory stick, CD-ROM,RAM, ROM, etc., or a collection thereof) can also be provided (e.g., incommunication with the processing arrangement). The computer-accessiblemedium 103 can contain executable instructions 104 thereon. In additionor alternatively, a storage arrangement 105 can be provided separatelyfrom the computer-accessible medium 103, which can provide theinstructions to the processing arrangement 101 so as to configure theprocessing arrangement to execute certain exemplary procedures,processes and methods, as described hereinabove, for example.

Further, the exemplary processing arrangement 101 can be provided withor include an input/output arrangement 106, which can include, e.g., awired network, a wireless network, the internet, an intranet, a datacollection probe, a sensor, etc. The exemplary processing arrangement101 can be in communication with an exemplary display arrangement 107,which, according to certain exemplary embodiments of the presentdisclosure, can be a touch-screen configured for inputting informationto the processing arrangement in addition to outputting information fromthe processing arrangement, for example. Further, the display and/or astorage arrangement can be used to display and/or store data in auser-accessible format and/or user-readable format.

Of special interest are the blood constituents oxy-hemoglobin (Hb02) anddeoxy hemoglobin (Hb), which have distinctly different absorptionspectra in the visible and near-infrared wavelength region. Byperforming measurements at multiple wavelengths, concentration of thesechromophores as well as parameters such as total hemoglobin11−1bT1=11−1b021+[Hb] or oxygensaturation St02=11−1b021/1HbT1 can bederived. Using advanced tomographic image reconstruction codes 2- and3-dimensional maps of these and other parameters, such as blood volume,can be generated.

The foregoing merely illustrates the principles of the disclosure.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.It will thus be appreciated that those skilled in the art will be ableto devise numerous systems, arrangements, and procedures which, althoughnot explicitly shown or described herein, embody the principles of thedisclosure and can be thus within the spirit and scope of thedisclosure. In addition, all publications and references referred to canbe incorporated herein by reference in their entireties. It should beunderstood that the exemplary procedures described herein can be storedon any computer accessible medium, including a hard drive, RAM, ROM,removable disks, CD-ROM, memory sticks, etc., and executed by aprocessing arrangement and/or computing arrangement which can be and/orinclude a hardware processors, microprocessor, mini, macro, mainframe,etc., including a plurality and/or combination thereof. In addition,certain terms used in the present disclosure, including thespecification, drawings and claims thereof, can be used synonymously incertain instances, including, but not limited to, e.g., data andinformation. It should be understood that, while these words, and/orother words that can be synonymous to one another, can be usedsynonymously herein, that there can be instances when such words can beintended to not be used synonymously. Further, to the extent that theprior art knowledge has not been explicitly incorporated by referenceherein, it can be explicitly being incorporated herein in its entirety.All publications referenced can be incorporated herein by reference intheir entireties.

Many alternatives, modifications, and variations are enabled by thepresent disclosure. Features of the disclosed embodiments can becombined, rearranged, omitted, etc. within the scope of the invention toproduce additional embodiments.

Furthermore, certain features of the disclosed embodiments may sometimesbe used to advantage without a corresponding use of other features.Accordingly, Applicants intend to embrace all such alternatives,modifications, equivalents, and variations that are within the spiritand scope of the present disclosure.

While embodiments and applications of this invention have been shown anddescribed, it would be apparent to those skilled in the art that manymore modifications are possible without departing from the inventiveconcepts herein. The invention is not limited to the description of theembodiments contained herein, but rather is defined by the claimsappended hereto and their equivalents. For example, the disclosedsubject matter includes various structures and methods as appliedprincipally to the problem of diagnosing or screening for vasculardisease. However, the same may be applied to other types of diagnosticproblems and/or body parts with relatively minor modification or nomodification at all.

1. An optical tomography imaging system for detecting peripheral arterydisease, comprising: an external body part stimulator that selectivelyapplies a mechanical stimulus to a target body part to be inspected; aninterfacing module arranged to contact the body part and image a portionof the body part using a plurality of light sources and a plurality oflight detectors; and a controller programmed to control each of theplurality of light sources to emit light sequentially such that light istransmitted through the body part and transmitted light is detected bythe plurality of light detectors, selectively activate the external bodypart stimulator to apply a first mechanical stimulus while acquiring afirst series of time separated data from the light detected by theplurality of light detectors, subsequently selectively activate theexternal body part stimulator to apply a second mechanical stimuluswhile acquiring a second series of time separated data from the lightdetected by the plurality of light detectors, generate first crosssectional tomographic image data representing the body part based on thefirst series of time separated data, and generate second cross sectionaltomographic image data representing the body part based on the secondseries of time separated data, and compare the first cross sectionaltomographic image data to the second cross sectional tomographic imagedata.
 2. The system of claim 1, wherein the external body partstimulator is a compression applicator.
 3. The system of claim 2,wherein the external body part stimulator is a pressure cuff.
 4. Thesystem of claim 1, wherein the first cross sectional tomographic imagedata representing the body part and the second cross sectionaltomographic image data representing the body part represent perfusionrates of blood.
 5. The system of claim 1, wherein the first crosssectional tomographic image data representing the body part and thesecond cross sectional tomographic image data representing the body partrepresent hemoglobin concentrations.
 6. The system of claim 1, whereinthe first cross sectional tomographic image data representing the bodypart and the second cross sectional tomographic image data representingthe body part represent volume of blood.
 7. The system of claim 1,wherein the plurality of light sources are configured to emit nearinfrared light.
 8. The system of claim 1, wherein the plurality of lightsources are configured to emit selectable wavelengths and the controlleris configured to emit different wavelengths simultaneously.
 9. Thesystem of claim 1, wherein the plurality of light sources and theplurality of light detectors include optical fibers.
 10. The system ofclaim 9, wherein the optical fibers are in direct contact with the bodypart. 11.-13. (canceled)
 14. An optical tomography imaging method fordetecting peripheral arterial disease in a body part of a subject,comprising: introducing the body part into an interfacing module, theinterfacing module including a plurality of light sources connected tolight conduits, and a plurality of detectors connected to a plurality oflight conduits, the interfacing module including a member shaped toenclose a portion of the body part, the plurality of light sources andthe plurality of light detectors being detachably attached to the memberso as to be positioned around the portion of the body part, theplurality of light sources and the plurality of light detectors beingpositioned on the member, wherein, in a first phase, each of theplurality of light sources sequentially emits light to be transmittedthrough the body part to be detected by the plurality of light detectorsto generate a first set of light transmission data, wherein, in a secondphase, each of the plurality of light sources sequentially emits lightto be transmitted through the body part to be detected by the pluralityof light detectors to generate a second set of light transmission data,wherein, in the first phase, the body part is exposed to a firstexternal stimulus and during the second phase the body part is exposedto a second external stimulus or no stimulus; reconstructing a firstspatial distribution of a hemoglobin concentration in the body partbased on the first set of light transmission data; reconstructing asecond spatial distribution of a hemoglobin concentration in the bodypart based on the second set of light transmission data; and comparingthe first spatial distribution of a hemoglobin concentration and to thesecond spatial distribution of a hemoglobin concentration.
 15. Themethod of claim 14, wherein the first external stimulus includespressure.
 16. The method of claim 15, wherein the first and second setsof light transmission data includes light intensity data.
 17. The methodof claim 15, wherein the pressure is applied to the body part byinflating a pressure cuff attached to a limb to which the body part isattached.
 18. The method of claim 17, wherein the pressure includes oneof diastolic and systolic pressures.
 19. The method of claim 14, furthercomprising differentiating between a sick and a healthy person based ona result of the comparing.
 20. The system of claim 1, wherein thecontroller is further programmed to differentiate between a sick and ahealthy person based on a result of the comparison between the firstcross sectional tomographic image data and the second cross sectionaltomographic image data.